Malignant transformation is accompanied by extensive cell-surface alterations. This project will employ immunochemical techniques to study spatial and temporal aspects of surface antigen expression during hepatocarcinogenesis. Conventional antisera and monoclonal antibodies will be used to characterize the cell-surface antigens of primary and transplantable hepatocellular carcinomas of ACI rats. The antigenic profiles of the tumor cells will be analyzed by two-dimensional electrophoresis of specific immunoprecipitates. The profiles of tumors will be compared with those of normal and regenerating hepatocytes to detect changes in expression of organ-specific antigens. Specific antibodies will be used to assess the contribution of fetal antigens and viral antigens to the total antigenic mosaic. Histocompatibility antigens will be subjected to extensive immunochemical and biochemical analysis to detect structural alterations. Immunofluorescence microscopy and cleavable bivalent cross-linking reagents will be used to examine topographic relationships of histocompatibility and tumor-associated antigens on the cell surface. Immunohistological methods will be used to examine livers of rats undergoing hepatocarcinogenesis for presence of tumor-associated antigens, and the serum of rats being fed hepatocarcinogens will be examined for presence of antigenic markers. These studies should provide insight into the role of surface structures in positional control and growth regulation and should contribute to our understanding of the relevance of altered-self recognition to tumor immunity.